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AMS Assay Performance |
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Determination of Assay Performance (Zoppi, 2007)
The performance of the Accium AMS instrument and Graphite Preparation Laboratory was assessed in a series of validation tests carried out in accordance with the "Good Laboratory Practice for Nonclinical Laboratory Studies" (GLP) quality system (U.S. Food and Drug Administration, 21 CFR58). Precision and accuracy were first determined for the AMS instrument by measuring IAEA-C6 and IAEA-C7 certified reference standard (Le Clercq et al. 1998), as well as HOxI, and HOxII standards (Stuiver 1993) prepared at the Australian Nuclear Science and Technology Organization (ANSTO) (Fink et al. 2004). For each standard, the graphite was pooled and thoroughly mixed before being loaded into different cathode holders. Three IAEA-C7 cathodes were each measured 3 times for 120 seconds and normalized against HOxI and HOxII standards and their results combined into a single mean value. The whole measurement sequence was repeated on 3 consecutive days. Summary Samples were readily measured with 0.3% precision and accuracy, machine background levels were consistently in the low 10–16 (14C/12C), and chemical background was approximately equivalent to a fraction of modern of 0.004. In addition, when 100-times-modern samples were processed, no increase in background was observed, either during sample processing or during AMS measurement. This corresponds to a dynamic range for 14C analysis of 6 orders of magnitude. Relevant Units 1 Fraction Modern = 13.56 DPM/g carbon 1 Fraction Modern = 6.11 fCi/mg carbon 1 Fraction Modern = 97.9 attomole 14C/mg carbon
Results |
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Comparison between measured and certified 14C concentrations for IAEA-C6 and IAEA-C7 standards prepared at Accium BioSciences. Samples were measured to within + 0.5% of certified values. By comparison, the reference standards have an equivalent 14C concentration equal to 0.308 and 0.924 DPM/mL plasma.
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A known amount of 14C was added to a series samples to create a range of 14C concentration. Linearity was assessed by comparing the AMS measured value to the known (calculated) value across a range of 0.1 - 150 fraction modern. This is approximately equal to 0.123 - 124 DPM/mL plasma.
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Comparison of measured 14C concentrations for a series of duplicate samples demonstrates excellent reproducibility over an unprecedented 6 orders of magnitude.
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AMS sensitivity can be measured in several ways. One of the more useful ways of expressing AMS sensitivity is to demonstrate detection of a very small amount of 14C-labled material spiked into an unlabeled biological matrix (plasma) or extract (HPLC fraction). Accium's AMS system reliably quantifies 0.01 DPM with a precision of 5% or better. We are also able to detect down to 0.001 DPM external signal (drug) above the assay background by using assay carriers with very low background signal. Please contact our technical team to specifically determine the AMS sensitivity for your molecule under the planned study conditions.
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Measured 14C concentrations for 2 "hot" samples followed by machine and chemical blanks demonstrate that there is no measurable cross-contamination. The measurement sequence (left to right) corresponds to the sequence in the sample processing laboratory.
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Reference Le Clercq M, van der Plicht J, Gröning M. 1998. New 14C reference materials with activities of 15 and 50 pMC. Radiocarbon 40(1):295–7. Stuiver M. 1983. International agreements and the use of the new oxalic acid standards. Radiocarbon 25(2): 793–5. Fink D, Hotchkis M, Hua Q, Jacobsen G, Smith AM, Zoppi U, Child D, Mifsud C, van der Gaast H, Williams A, Williams M. 2004. The ANTARES AMS facility at ANSTO. Nuclear Instruments and Methods in Physics Research B 223–224:109–15. Zoppi, U. , J. Crye, Q. Song, A. Arjomand. Performance Evaluation of New Accelerator Mass Spectrometer at Accium BioSciences, Radiocarbon, Vol 49, Nr1, 2007, p 171-180.
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Copyright © Accium BioSciences, Inc. 2004-2007 |
